PROJECT SUMMARY Taste buds are the sensory end organs of the gustatory system, and contain elongate cells that detect five basic taste qualities: bitter, sweet, umami, sour, and salty. In recent years, much progress has been made in understanding how taste receptor cells detect and process these taste qualities. Much less is known, however, about the communication of this information from the periphery to the central nervous system, where it can influence food preferences and, ultimately, food intake. In particular, Type III taste receptor cells are poorly understood in terms of signaling to afferent nerve fibers as well as neighboring cells in the taste bud. Type III taste cells are sensitive to sour and salty stimuli (Huang et al., 2006; Oka et al., 2013). The application of acids (sour) to intact or semi-intact taste buds causes intracellular acidification in all taste cells, complicating results from such experiments via non-specific effects of acids on Type I or Type II cells. Our understanding of Type III cell specific function is thus limited to isolated cell studies. To circumvent this challenge, our laboratory has generated a mouse that expresses Cre recombinase in a population of Type III taste cells, allowing us to drive the expression of light-activated cation channel channelrhodopsin in Type III taste cells throughout the oral cavity. With this mouse, I can activate Type III taste cells directly with light, rather than acid, avoiding non- specific effects of acid on neighboring taste receptor cells. This proposal outlines my plans to use this mouse to address two major questions of Type III cell function: (1) which neurotransmitters carry the signal from Type III taste cells to afferent nerve fibers? and (2) do Type III cells participate in a communication circuit with neighboring Type II cells that ultimately modulates the overall taste bud output to afferent nerves? My results will provide new insight into the transmission of tastant information from the taste bud to the central nervous system, ultimately deepening our understanding of the system as a whole.